Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure

Author(s):Show less -

Diaz, Hugo S. ^[1] ; Andrade, David C. ^{[1, 2]} ; Toledo, Camilo ^{[1, 3]} ; Pereyra, V, Katherin ; Schwarz, Karla G. ^[4] ; Diaz-Jara, Esteban ^[4] ; Lucero, Claudia ^[4] ; Arce-Alvarez, Alexis ^[4] ; Schultz, Harold D. ^[5] ; Silva, Josiane N. ^[6] ; Takakura, Ana C. ^[6] ; Moreira, Thiago S. ^[7] ; Marcus, Noah J. ^[8] ; Del Rio, Rodrigo ^{[3, 9, 4]}

Affiliation

^[1] Pontificia Univ Catolica Chile, Dept Physiol, Lab Cardioresp Control, Santiago - Chile

^[2] Univ Mayor, CIFE, Santiago - Chile

^[3] Pontificia Univ Catolica Chile, Ctr Envejecimiento & Regenerac CARE UC, Santiago - Chile

^[4] Pereyra, Katherin, V, Pontificia Univ Catolica Chile, Dept Physiol, Lab Cardioresp Control, Santiago - Chile

^[5] Univ Nebraska Med Ctr, Dept Cellular & Integrat Physiol, Omaha, NE - USA

^[6] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[8] Des Moines Univ, Dept Physiol & Pharmacol, Des Moines, IA - USA

^[9] Univ Magallanes, Ctr Excelencia Biomed Magallanes CEBIMA, Punta Arenas - Chile

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY; v. 318, n. 1, p. L27-L40, JAN 2020.
• Web of Science Citations: 0

Abstract

Enhanced central chemoreflex (CC) gain is observed in volume overload heart failure (HF) and is correlated with autonomic dysfunction and breathing disorders. The aim of this study was to determine the role of the CC in the development of respiratory and autonomic dysfunction in HF. Volume overload was surgically created to induce HF in male Sprague-Dawley rats. Radiotelemetry transmitters were implanted for continuous monitoring of blood pressure and heart rate. After recovering from surgery, conscious unrestrained rats were exposed to episodic hypercapnic stimulation {[}EHS; 10 cycles/5 min, inspiratory fraction of carbon dioxide (FICO2) 7%] in a whole body plethysmograph for recording of cardiorespiratory function. To determine the contribution of CC to cardiorespiratory variables, selective ablation of chemoreceptor neurons within the retrotrapezoid nucleus (RTN) was performed via injection of saporin toxin conjugated to substance P (SSP-SAP). Vehicle-treated rats (HF+Veh and Sham+Veh) were used as controls for SSP-SAP experiments. Sixty minutes post-EHS, minute ventilation was depressed in sham animals relative to HF animals (Delta V-E: -5.55 +/- 2.10 vs. 1.24 +/- 1.35 mL/min 100 g, P < 0.05; Sham+Veh vs. HF+Veh). Furthermore, EHS resulted in autonomic imbalance, cardiorespiratory entrainment, and ventilatory disturbances in HF+Veh but not Sham+Veh rats, and these effects were significantly attenuated by SSP-SAP treatment. Also, the apneahypopnea index (AHI) was significantly lower in HF+SSP-SAP rats compared with HF+Veh rats (AHI: 5.5 +/- 0.8 vs. 14.4 +/- 1.3 events/h, HF+SSP-SAP vs. HF+Veh. respectively. P < 0.05). Finally. EHS-induced respiratory-cardiovascular coupling in HF rats depends on RTN chemoreceptor neurons because it was reduced by SSP-SAP treatment. Overall. EHS triggers ventilatory plasticity and elicits cardiorespiratory abnormalities in HF that are largely dependent on RTN chemoreceptor neurons. (AU)

• FAPESP's process: 16/22069-0 - Amelioration of the brainstem vascular imbalances in an spontaneously hypertensive rats with exercise
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/23281-3 - Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson's Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants